Nemo-like kinase (NLK) negatively regulates NF-kappa B activity through
disrupting the interaction of TAK1 with IKK?
#MMPMID24721172
Li SZ
; Zhang HH
; Liang JB
; Song Y
; Jin BX
; Xing NN
; Fan GC
; Du RL
; Zhang XD
Biochim Biophys Acta
2014[Jul]; 1843
(7
): 1365-72
PMID24721172
show ga
Stringent negative regulation of the transcription factor NF-?B is essential for
maintaining cellular stress responses and homeostasis. However, the tight
regulation mechanisms of IKK? are still not clear. Here, we reported that
nemo-like kinase (NLK) is a suppressor of tumor necrosis factor (TNF?)-induced
NF-?B signaling by inhibiting the phosphorylation of IKK?. Overexpression of NLK
largely blocked TNF?-induced NF-?B activation, p65 nuclear localization and I?B?
degradation; whereas genetic inactivation of NLK showed opposing results.
Mechanistically, we identified that NLK interacted with I?B kinase
(IKK)-associated complex, which in turn inhibited the assembly of the TAK1/IKK?
and thereby, diminished the I?B kinase phosphorylation. Our results indicate that
NLK functions as a pivotal negative regulator in TNF?-induced activation of NF-?B
via disrupting the interaction of TAK1 with IKK?.
|Cell Nucleus/drug effects/metabolism
[MESH]
|Gene Expression Regulation
[MESH]
|HCT116 Cells
[MESH]
|HEK293 Cells
[MESH]
|Humans
[MESH]
|I-kappa B Kinase/genetics/*metabolism
[MESH]
|Intracellular Signaling Peptides and Proteins/antagonists &
inhibitors/genetics/*metabolism
[MESH]
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